A method of synthesizing a crystalline molecular sieve having an MSE framework type comprises crystallizing a reaction mixture comprising a source of water, a source of an oxide of a tetravalent element, Y, selected from at least one of silicon, tin, titanium, vanadium, and germanium, optionally a source of a trivalent element, X, a source of an alkali or alkaline earth metal, M, and a source of organic dications, Q, such as 3-hydroxy-1-(4-(1-methylpiperidin-1-ium-1-yl)butyl)quinuclidin-1-ium, 3-hydroxy-1-(5-(1-methylpiperidin-1-ium-1-yl)pentyl)quinuclidin-1-ium, 1,1'-(butane-1,4-diyl)bis(1-methylpiperidin-1-ium), 1,1'-(pentane-1,5-diyl)bis(1-methylpiperidin-1-ium), 1,1'-(hexane-1,6-diyl)bis(1-methylpiperidin-1-ium), and 1,1'-((3as,6as)-octahydropentalene-2,5-diyl)bis(1-methylpiperidin-1-ium).

The invention provides a process of preparing an intermediate useful in the synthesis of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester, and a process of preparing a crystalline freebase of the ester.

A process for preparing the compound of the following formula (E): wherein Bn represents a benzyl group, and tBu represents a tert-butyl group, the process including: (a) subjecting the following compound (B) to trifluoroacetylation, wherein tBu represents a tert-butyl group to produce the following compound (C): wherein tBu represents a tert-butyl group, and TFA represents a trifluoroacetyl group; (b) reacting the compound (C) with benzyloxyamine in the presence of a hydroxyl group activating agent to produce the following compound (D): wherein Bn represents a benzyl group, tBu represents a tert-butyl group, and TFA represents a trifluoroacetyl group; and (c) subjecting the compound (D) to detrifluoroacetylation.

This invention relates to novel compounds which are inhibitors of the Rearranged during Transfection (RET) kinase, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy, alone or in combination, for the normalization of gastrointestinal sensitivity, motility and/or secretion and/or abdominal disorders or diseases and/or treatment related to diseases related to RET dysfunction or where modulation of RET activity may have therapeutic benefit including but not limited to all classifications of irritable bowel syndrome (IBS) including diarrhea-predominant, constipation-predominant or alternating stool pattern, functional bloating, functional constipation, functional diarrhea, unspecified functional bowel disorder, functional abdominal pain syndrome, chronic idiopathic constipation, functional esophageal disorders, functional gastroduodenal disorders, functional anorectal pain, inflammatory bowel disease, proliferative diseases such as non-small cell lung cancer, hepatocellular carcinoma, colorectal cancer, medullary thyroid cancer, follicular thyroid cancer, anaplastic thyroid cancer, papillary thyroid cancer, brain tumors, peritoneal cavity cancer, solid tumors, other lung cancer, head and neck cancer, gliomas, neuroblastomas, Von Hippel-Lindau Syndrome and kidney tumors, breast cancer, fallopian tube cancer, ovarian cancer, transitional cell cancer, prostate cancer, cancer of the esophagus and gastroesophageal junction, biliary cancer, adenocarcinoma, and any malignancy with increased RET kinase activity.

A description is given of N-(1,2,5-oxadiazol-3-yl)pyridinecarboxamides of the general formula (I) as herbicides. R in this formula (I) stands for radicals such as hydrogen, organic radicals, and other radicals such as halogen. W stands for a substituted pyridyl radical.

The present invention is directed to ethanamine compounds, pharmaceutical compositions comprising the same, and methods of treating depression by administering the ethanamine compound.

The invention relates to compounds represented by Structural Formula I, which can bind to CCR9 receptors and block the binding of a ligand (e.g., TECK) to the receptors. The invention also relates to a method of inhibiting a function of CCR9, and to the use compounds represented by Structural Formula I in research, therapeutic, prophylactic and diagnostic methods.

The present invention relates to novel synthetic substituted heterocyclic compounds and pharmaceutical compositions containing the same that are capable of inhibiting or antagonizing a family of receptor tyrosine kinases, Tropomysosin Related Kinases (Trk), in particular the nerve growth factor (NGF) receptor, TrkA. The invention further concerns the use of such compounds in the treatment and/or prevention of pain, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, or a disease, disorder or injury relating to dysmyelination or demyelination or the disease or disorder associated with abnormal activities of NGF receptor TrkA.

A method of manufacturing an anhydrous copper complex of formula C12H10CICuN2O4 and methods of treating neuromuscular and other diseases, including but not limited to fibromyalgia, multiple sclerosis, muscular dystrophy, rheumatoid arthritis, pain, fatigue, sleeplessness, loss of fine motor control, speech loss, inflexibility, Alzheimer's, dementia, amyotrophic lateral sclerosis, depression, lyme disease, lyme disease co-infection, gastroparesis (GP), myopathy, chronic inflammation and/or incontinence. The anhydrous copper complex preferably is administered in a pharmaceutical and/or dietary supplement composition of the invention.

This invention relates to compounds of general formula (I) in which R1, R2, U, V, L, M, R5, m, X, Y and Z are as defined herein, and the pharmaceutically acceptable salts thereof, to pharmaceutical compositions comprising such compounds and salts, and to methods of using such compounds, salts and compositions for the treatment of abnormal cell growth, including cancer.

This disclosure is directed to fused tetracyclic pyrido[4,3-b>]indole and pyrido[3,4-b]indole derivatives. Pharmaceutical compositions comprising the compounds are also provided, as are methods of using the compounds in a variety of therapeutic applications, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or a neuronal disorder.

The present invention generally relates to use of compounds and compositions as a chemosensitizers and/or radiosensitizers and/or inhibitors of PNKP phosphatase activity. The present invention provides pharmaceutical combinations and/or a pharmaceutically acceptable salt thereof, kits containing such compounds and/composition and methods of using such compounds and/or compositions.

The present invention provides a process for the synthesis of substituted phenoxymethylpropionic acid and related compounds. The compounds are useful for inhibiting the formation of AGEs (Advanced Glycation End Products).

Disclosed are solid forms of 8-chloro-N-[(2-chloro-5-methoxyphenyl)sulfonyl]-6-(trifluoromethyl)-imidazo[1,2-a]pyridine-2-carboxamide (Compound 1). Methods for the preparation of solid forms of Compound 1 and for the conversion of one solid form of Compound 1 into another are disclosed. Disclosed are nematocidal compositions comprising a nematocidally effective amount of a solid form of Compound 1 and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid carriers. Compositions comprising a mixture of a solid form of Compound 1 and at least one other nematicide, insecticide and/or fungicide are also disclosed.Also disclosed are methods for protecting a plant from nematodes comprising applying to the plant, or portion, or seed thereof, or to the growing medium of the plant, a nematocidally effective amount of Compound 1 comprising the polymorph Form A.

The present invention provides compounds having the general structural formula (I), and pharmaceutically acceptable derivatives thereof, as described generally and in classes and subclasses herein, and additionally provides pharmaceutical compositions thereof, and methods for the use thereof for the treatment of any of a number of conditions or diseases involving abnormal or excessive fibrosis.

The invention is directed to novel substituted benzylamino quinolines, compounds comprising substituted benzylamino quinolines, methods of making substituted benzylamino quinolines, the use of substituted benzylamino quinolines for treating or preventing a variety of conditions or diseases associated with lipoprotein metabolism, and the use of substituted benzylamino quinolines as cholesterol ester-transfer protein inhibitors.

Many GTPases such as Ras, Ral and Rho require post-translational farnestylation or geranylgeranylation for mediating malignant transformation. Dual farnesyltransferase (FT) (FTI) and geranylgeranyltransferase-I (GGT-1) inhibitors (GGTI) were developed as anticancer agents from based on an ethylenediamine scaffold. On the basis of a 4-fold substituted ethylenediamine scaffold, the inhibitors are structurally simple and readily derivatized, facilitating extensive structure-activity relationship studies. The most potent inhibitor is compound exhibited an in vitro hFTase IC50 value of 25 nM and a whole cell H-Ras processing IC50 value of 90 nM. Several of the inhibitors proved highly selective for hFTase over the related prenyltransferase enzyme geranylgeranyltransferase-I (GGTase-I). A crystal structure of an inhibitor cocrystallized with farnesyl pyrophosphate in the active site of rat FTase illustrates that the para-benzonitrile moiety is stabilized by a π-π stacking interaction with the Y361β residue, suggesting an importance of this component of the inhibitors.

There are provided compounds of formula (I), wherein R1, R6, R8, Q2, Q3, Q3a, Q4, L and A have meanings given in the description, and pharmaceutically-acceptable salts thereof, which compounds are useful in the treatment of diseases in which inhibition of the activity of a member of the MAPEG family is desired and/or required, and particularly in the treatment of inflammation and/or cancer.

The present invention relates to the use of selective adenosine A1 agonists, in particular the dicyanopyridines of formula (I), for the treatment and/or prophylaxis of glaucoma and ocular hypertension as well as the their use for the production of a medicament for the treatment and/or prophylaxis of glaucoma and ocular hypertension.

This invention relates to a method of preparing a benzoimidazole derivative at high purity and high yield so as to enable the production of the benzoimidazole derivative compound as an antagonist against a vanilloid reactor-1, and particularly to a method of preparing a benzoimidazole derivative at high purity and high yield, wherein the benzoimidazole derivative is synthesized using a novel intermediate, namely, benzaldehyde, and thereby the preparation process is simple so that it can be applied to production.

Compounds according to Formula I and Formula II are potent inhibitors of Arginase I and II activity: where R1, R2, R3, R4, R5, R6, R7, R8, R9, D, M, X, and Y are defined as set forth in the specification. The invention also provides pharmaceutical compositions of the compounds and methods of their use for treating or preventing a disease or a condition associated with arginase activity.

Herein are disclosed fluorescent dyes based around a framework for a ligand comprising a pyridyl group linked to a diaryl anilido unit. A variety of ligands based on this framework are disclosed. The ligands chelate to a BF2 center to produce the fluorescent dye. The disclosed dyes combine longer Stokes shifts (approximately 100 nm) with increased quantum yields. They are also photostable in aqueous and organic solutions for several hours. These dyes may be used in the labeling of biomolecules for bioimaging and assays. Also disclosed are methods for the synthesis of these dyes.

The present invention provides processes for the preparation of saturated ketone morphinan compounds. In particular, the invention provides processes for the conversion of a morphinan comprising an allyl alcohol ring moiety into a morphinan comprising a saturated ketone ring moiety by an isomerization reaction catalyzed by an inorganic salt of a late transition metal.

The invention provides novel inhibitors of IAP that are useful as therapeutic agents for treating malignancies where the compounds have the general formula I: wherein A, Q, X1, X2, Y, R1, R2, R3, R4, R4', R5, R6 and R6' are as described herein.

The present invention relates to novel bicyclic thiazoles which are positive allosteric modulators of the metabotropic glutamate receptor subtype 5 (“mGluR5”) and which are useful for the treatment or prevention of disorders associated with glutamate dysfunction and diseases in which the mGluR5 subtype of receptors is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which mGluR5 is involved.

The present invention relates to a novel method for producing a pyridazinone compound and an intermediate thereof as shown in the following scheme: wherein the symbols are as defined in the specification.

Disclosed are compounds which inhibit the activity of anti-apoptotic Bcl-2 or Bcl-xL proteins, compositions containing the compounds and methods of treating diseases during which are expressed anti-apoptotic Bcl-2 protein.

The present invention is concerned with a process for preparing 5-(2{[6-(2,2-difluoro-2-phenylethoxy)hexyl]amino}-1(R)-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one or a pharmaceutically acceptable salt thereof.

An objective of the present invention is to provide a process for producing 4-carbonyl oxyquinoline derivatives useful as agricultural and horticultural pesticides and fungicides. The objective can be attained by a process for producing 4-carbonyl oxyquinoline derivatives represented by general formula (1), the process including reacting a quinolone derivative with a halogenated compound or an acid anhydride in the presence of a phase transfer catalyst and a base.

A fastening assembly includes a connecting member, a mounting member mounted to the connecting member, and a sliding member. The mounting member includes a first fixing portion. The sliding member is slidably received in the mounting member and the connecting member. The sliding member includes a first end exposed out of the first fixing portion, and a second end slidably received in the connecting member. The second end of the sliding member is operable to be extended out of or substantially coplanar with an end of the connecting member. The fastening assembly can be utilized to mount a heat sink to a board.

The invention includes a method, and a component made according to the method having at least one thread pattern formed thereon from a stamping method. The invention includes a tubular member comprising a body having a wall formed from a wrapped sheet of stock to define an interior wall and an exterior wall, a seam in the wall defining a first and second end of the wrapped sheet of stock, and a thread pattern stamped on the exterior wall. The method comprises the steps of forming a blank from sheet of stock having a first surface. A thread pattern is formed onto the first surface while in a substantially sheet-like form. A bending operation then forms the sheet stock into a tubular member such that the thread pattern, located on the tube's external surface, is substantially aligned about its circumference.

An electronic device includes, a circuit board including a through hole, a member including a screw hole, a screw including a screw body having an outer diameter smaller than an inner diameter of the through hole and a screw head having an outer diameter larger than the inner diameter of the through hole, wherein the screw body penetrates through the through hole to engage with the screw hole and the screw head is disposed on an opposite side of the circuit board to the member, and a first washer provided between the screw head and the circuit board, the first washer including a first washer body and a plurality of first washer legs extending from the first washer body toward the circuit board, the first washer legs being in contact with the circuit board and having a characteristic of reducing stress on the circuit board upon being heated.

A method of manufacturing fastenings or fasteners with radial outer contours, especially screws or threaded bolts, made of solid metal is performed by a device. The method manufactures the fastenings or fasteners preferably on a multi-stage press. Several recesses running in an axial direction at a fixed radial distance are formed in the shank-shaped section of a blank. The prefabricated blank with the recesses is inserted into a multi-part split mold within a multi-stage press, whose die stocks have an inner profiling forming the outer contour, and are opened in the starting position, that at the places where the die stocks are opened, there are the recesses. During the closing movement of the die stocks, at least one radial outer contour is pressed on the shank-shaped section of the blank by radial action of forces, with the recesses preventing material from getting between the die stocks during the pressing process.

The theft-protected screw part in the form of a nut or a screw has a free end region and a ring-shaped depression formed at the end region for the engagement of a wrench for rotation the screw part. Viewed from radially outside to radially inside, the depression is delimited by an outer edge, a bottom and an inner edge. The outer edge forms outer abutment surfaces and the inner edge forms inner abutment surfaces for the wrench. The screw part is composed of a main part and an insert. The main part has a protrusion, which is located within the inner edge. The insert is designed in a ring shape, has a hole for accommodating the protrusion and forms the inner abutment surfaces.

The present invention is premised upon method of manufacturing rolled pierce nuts having a predetermined profile from a metal rod, more particularly to a method and apparatus delivering greater manufacturing flexibility through the use of multiple stations with flexible inputs and outputs.

The present invention provides a method for manufacturing a fitting that has a configuration where a fitting plate and a blind nut are integrally formed and also provides a tap tool for use in this method. According to the present invention, performing tap processing to an internal diameter portion to integrally form a portion corresponding to the blind nut, when a tap tool having a protrusion at an end thereof is utilized to be inserted into the bag-like blind hole at a planned part of the blind nut and the tap processing is carried out, the protrusion provided at the end of the tap tool comes into contact with an inner wall at the end of the bag-like blind hole, and a pressed material thereby forms a convex shape on an outer side of the bag-like blind hole.

A magnetized nut for fastening a compressor wheel of an exhaust turbocharger to a turbo shaft. The nut has a base body made of a non-magnetic material forming a hollow space for accommodating a magnetic material, and a method for the production of the magnetized nut. In order to provide a magnetized nut that is produced in a simple and cost-effective manner and ensures as equal a distribution of mass as possible with regard to the rotational axis of the nut, the magnetic material is introduced into the hollow space using injection molding.

There is provided a nut having a thread portion having a female thread, a metallic plate portion having a base segment, and a hardness gradient portion provided between the thread portion and the metallic plate portion. The thread portion, metallic plate portion and the hardness gradient portion are monolithic each other, a metallographic structure of the metallic plate portion differs from a metallographic structure of the thread portion and a hardness of the hardness gradient portion is lower than a hardness of the thread portion and lowers from the thread portion toward the metallic plate portion.

A thread forming tap having a complete thread portion, formed with a predetermined back taper with that decreases rotational torque during tapping work, which reduces load acting on first complete protruding portions, formed at an extreme leading end of the complete thread portion, and thereby suppressing degradation in service life of the tool due to wear.

The invention relates to a profile-rolling machine for rolling a profile in a blank, wherein the profile-rolling machine has a first and a second profile-rolling jaw. The second profile-rolling jaw (126) is guided—held by a carriage (124)—in a guide track (130) relative to the first profile-rolling jaw (110) for the purpose of rolling the profile into the blank. The carriage (124) has a carriage slide plate (122) and the guide track (130) has a guide slide plate (132). The two slide plates together form a sliding pairing and slide on each other. In order to render said sliding pairing less susceptible to dirty lubricant and less susceptible to wear, it is proposed according to the invention to manufacture the guide slide plate (132) and/or the carriage slide plate (122) at least partially from ceramic or from a non-metallic material or to coat the same with such materials.

A rolling machine comprises parallel guides delimiting a workpiece conveying channel extending from a plurality of per se known rolling tools to a machined workpiece unloading arrangement, wherein, upstream of the workpiece unloading arrangement, one of the channel delimiting guides is operatively coupled to a structural element swingably supported by a pivot pin, the structural element being integral with the piston rod of a cylinder-piston unit slidably driving the structural element together with the channel delimiting guide, thereby providing a side unloading opening for the workpiece.

A full-round head nail having an offset head is configured with a gusset formed integrally between an undersurface of the offset head and a superior portion of a shank. The head of the nail is relatively thin, and the shank is positioned radially off center of the round head such that no heel is formed at a point tangential to both the head and the shank. The gusset has a lofted surface tapering radially from a roundness at the zero heel to a taper at the toe. The gusset reinforces the junction of the shank with the head, supports the toe of the head, and distributes the force of a load on the head through a longitudinal axis of the shank, preventing the toe from bending or yielding and prevents the shank from yielding to the stresses of the load applied.

A set of tooling for making pointed headed bolts of a given diameter in numerous lengths with roll thread ready threaded to the head and partially threaded shanks in a four forming station forming machine, the tools being configured to work on wire stock as received at the first station of a diameter larger than or substantially the same as the roll diameter and not greater than the nominal diameter of the bolt, including at least two sequential head forming tools for mounting on the slide, an extrusion pointing tool for mounting on the die breast, a roll diameter extrusion tool for mounting on the die breast and a head support tool mountable in a station on the slide at multiple axial positions corresponding to standard lengths of the bolts being made, the head support tool being arranged to work at either the extrusion pointing station or the roll diameter extrusion station.

Provided is a method for manufacturing an FRP member with insert which enables to reduce a machining time to improve productivity. First, a threaded hole 11 is formed in an insert 3. An FRP member 2 where at least the threaded hole 11 of the insert 3 is covered with a coating 4 made of FRP is molded. A counter-bored hole 31 that penetrates the coating 4 of the FRP member 2 to communicate with the threaded hole 11 of the insert 3 is formed, to thereby obtain an FRP component 1 with insert. Accordingly, a machining step after molding the FRP member 2 in which dry machining is required includes only the boring step of forming the counter-bored hole 31 in the FRP member 2. Thus, the machining time can be reduced, and the productivity can be improved.

In FIG. 2, a diameter Dd of drilling edges of a drill is selected smaller than a valley diameter d1 of a male thread of a tap portion, and an inner diameter D1 of a female thread is defined by the valley diameter d1 of the male thread. Therefore, a predetermined radial gap is formed between the male thread 30 formed by the tap portion and the drill. When a tap with the drill is reversely rotated to be pulled out from the female thread after cutting the female thread, the tap released from the restriction may deflectively displace in the diameter direction upon pulling out the male thread of the tap portion from the female thread. However, the drill hardly contacts with the female thread, so that the occurrence of the defective product due to the contact is suppressed.

Techniques for reinforcing concrete using rebar are disclosed. Some example embodiments may include prestressed concrete structures reinforced by twisted, threaded reinforcing bars. An example reinforcing bar for a prestressed concrete structure may include an elongated, generally cylindrical rod; an external thread disposed on the generally cylindrical rod, the external thread formed from an elongated, generally nonlinear channel wrapped about a radial surface of the generally cylindrical rod in a generally helical fashion. A base portion of the nonlinear channel may be disposed substantially against the radial surface of the generally cylindrical rod and/or an upstanding portion of the nonlinear channel may extend generally orthogonally from the radial surface of the generally cylindrical rod.

Disclosed is a tap driver and tap driver system for rigid tapping, which includes a unique flexure system. In some embodiments, an integrated flexure component and housing configuration provides and may provide both a more economical and a universal configuration of the tap driver flexure component that allows the central body to be integrated with and into different types of tap drivers.

A form tap for tapping an article may include a longitudinal shank having a mounting end opposite a tip, the shank having a shank length, and a thread portion with a plurality of threads for engaging a surface of the article. The thread portion includes a first region, a second region and a third region. The form tap includes a plurality of lobes extending though the first and second regions from the tip to the second region end, the lobes being spaced circumferentially around the shank and lying on a crest circumference. Each lobe may be disposed between respective first and second convex relief portions and each relief portion may be spaced radially inward from the crest circumference. Each lobe has a lobe width, the lobe width at the second region end being greater than the lobe width at the tip. The third region is free of lobes.

A clinch-type fastener is formed by simultaneously creating an undercut during the same forging that creates the head and displacer of the fastener. A fastener blank is compressed end-to-end between top and bottom dies whereby the axial compression of a blank causes the outward bulging of the shank at its midline. Simultaneously, a tapered end point and a tangential interference band are formed provided by a curvilinear-shaped bulge in the shank. As the bulge is formed an undercut is created between the bulge and a shoulder which extends downwardly from a head of the fastener. This method of formation and the fastener produced thereby are particularly suited to the manufacture of small clinch pins having a diameter in the range of 1.0 mm.

A testing method for the bolt to be used under the conditions of excessive wind force by which bolts made of Cr—Mo steel can be separated into a group of bolts usable in cold areas and a group of bolts unusable in cold areas without conducting Charpy impact test involving complicated operation, specifically, a testing method for determining whether bolts made of heat-treated Cr—Mo steel are usable or unusable in cold areas, wherein the determination is conducted on the basis of both J parameter calculated by formula: J=(Si %+Mn %) (P %+Sn %) 104 (wherein P %, Si %, Mn % and Sn % are contents (mass %) of phosphorus (P), silicon (Si), manganese (Mn) and tin (Sn) respectively as disclosed in the inspection certificate of the Cr—Mo steel) and bolt diameter.